Presence of fusobacterium nucleatum in relation to patient survival and an acidic environment in oesophagogastric junction and gastric cancers

ABSTRACT BACKGROUND _Fusobacterium nucleatum_ inhabits the oral cavity and affects the progression of gastrointestinal cancer. Our prior findings link _F. nucleatum_ to poor prognosis in

oesophageal squamous cell carcinoma via NF-κB pathway. However, its role in oesophagogastric junction and gastric adenocarcinoma remains unexplored. We investigated whether _F. nucleatum_

influences these cancers, highlighting its potential impact. METHODS Two cohorts of EGJ and gastric adenocarcinoma patients (438 from Japan, 380 from the USA) were studied. _F. nucleatum_

presence was confirmed by qPCR, FISH, and staining. Patient overall survival (OS) was assessed based on _F. nucleatum_ positivity. EGJ and gastric adenocarcinoma cell lines were exposed to

_F. nucleatum_ to study molecular and phenotypic effects, validated in xenograft mouse model. RESULTS In both cohorts, _F. nucleatum_-positive EGJ or gastric adenocarcinoma patients had

notably shorter OS. _F. nucleatum_ positivity decreased in more acidic tumour environments. Cancer cell lines with _F. nucleatum_ showed enhanced proliferation and NF-κB activation. The

xenograft model indicated increased tumour growth and NF-κB activation in _F. nucleatum_-treated cells. Interestingly, co-occurrence of _F. nucleatum_ and _Helicobacter pylori_, a known risk

factor, was rare. CONCLUSIONS _F. nucleatum_ can induce the NF-κB pathway in EGJ and gastric adenocarcinomas, leading to tumour progression and poor prognosis. Access through your

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BEING VIEWED BY OTHERS _FUSOBACTERIUM NUCLEATUM_ CONFERS CHEMORESISTANCE BY MODULATING AUTOPHAGY IN OESOPHAGEAL SQUAMOUS CELL CARCINOMA Article Open access 10 December 2020 _FUSOBACTERIUM

NUCLEATUM_ IS ASSOCIATED WITH WORSE PROGNOSIS IN LAUREN’S DIFFUSE TYPE GASTRIC CANCER PATIENTS Article Open access 01 October 2020 INTRATUMOUR _FUSOBACTERIUM NUCLEATUM_ AND IMMUNE RESPONSE

TO OESOPHAGEAL CANCER Article 04 January 2023 DATA AVAILABILITY The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable

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Scholar  Download references ACKNOWLEDGEMENTS We thank J. Iacona, Ph.D., from Edanz (https://jp.edanz.com/ac) for editing this manuscript. FUNDING This work was supported in part by

Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (grant numbers 17H04273, 17K19702, and 17KK0195 to Y.B.). AUTHOR INFORMATION AUTHORS AND

AFFILIATIONS * Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan Yoshihiro Hara, Yoshifumi

Baba, Eri Oda, Kazuto Harada, Kohei Yamashita, Tasuku Toihata, Keisuke Kosumi, Masaaki Iwatsuki, Yuji Miyamoto & Hideo Baba * Division of Translational Research and Advanced Treatment

Against Gastrointestinal Cancer, Kumamoto University, 1-1-1 Honjo, Chuoku, Kumamoto, 860-8556, Japan Yoshifumi Baba * Department of Gastrointestinal Medical Oncology, The University of Texas

MD Anderson Cancer Center, Houston, TX, USA Kohei Yamashita & Jaffer A. Ajani * Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo,

Chuo-ku, Kumamoto, 860-8556, Japan Hiroyasu Tsutsuki & Tomohiro Sawa * Department of Pathology, UT M. D. Anderson Cancer Center, Houston, USA Qiong Gan & Rebecca E. Waters *

Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan Yoshihiro Komohara Authors *

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Google Scholar * Hideo Baba View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS YH conducted experiments and contributed to manuscript writing.

YB provided guidance and supervision throughout the project. EO, KH, KY, TT, KK, MI, YM, and QG, REW were involved in data collection and analysis. HT and TS provided guidance on microbial

experimental techniques. YK assisted in the confirmation of pathological specimens. JAA and HB supervised the project. All authors contributed to the conception, design, and interpretation

of the study, and critically reviewed and approved the final manuscript. CORRESPONDING AUTHORS Correspondence to Yoshifumi Baba or Hideo Baba. ETHICS DECLARATIONS COMPETING INTERESTS The

authors declare no competing interests. ETHICS APPROVAL AND CONSENT TO PARTICIPATE Informed consent was obtained from all the participants. This study was conducted in accordance with the

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CITE THIS ARTICLE Hara, Y., Baba, Y., Oda, E. _et al._ Presence of _Fusobacterium nucleatum_ in relation to patient survival and an acidic environment in oesophagogastric junction and

gastric cancers. _Br J Cancer_ 131, 797–807 (2024). https://doi.org/10.1038/s41416-024-02753-0 Download citation * Received: 25 February 2024 * Revised: 24 May 2024 * Accepted: 05 June 2024

* Published: 12 July 2024 * Issue Date: 21 September 2024 * DOI: https://doi.org/10.1038/s41416-024-02753-0 SHARE THIS ARTICLE Anyone you share the following link with will be able to read

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